Efficient Synthesis of Protein-Polymer Conjugates with Open-Air Fabrication and Facile Purification Driven by the...

A simple, efficient, and broadly applicable method for the preparation of protein-polymer conjugates is of critical importance for their further development. However, existing approaches are often limited by challenges such as insufficient deoxygenation, complex purification processes, and poor compatibility of monomers and proteins. Herein, we present a comprehensive strategy for the synthesis of protein-polymer conjugates utilizing a thermosensitive, recyclable glucose oxidase-poly-(di-(ethylene glycol) methyl ether methacrylate) conjugate (GOX-PDEGMA) as part of the deoxygenation system. This strategy enables controlled polymerization under open-air conditions across volumes ranging from 10 μL to 100 mL, with the deoxygenation reagent being conveniently removed via phase transition postreaction. Notably, this strategy demonstrates excellent polymerization control, high retention of end-group, a straightforward and modular purification process, and compatibility with five different types of methacrylate monomers. It is also adaptable to a wide range of proteins, including antibodies, cytokines, and enzymes, while preserving their bioactivity. The development of this strategy not only expands the potential applications of protein-polymer conjugates in the synthesis of other conjugates but also unlocks new opportunities for their advanced use in biopharmaceuticals and related fields.